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lncRNA プロモーターによる遺伝子発現の局所的調節,転写およびスプライシング
Jesse M Engreitz1,2, Jenna E Haines1, Elizabeth M Perez1
1Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Nature
|November 4, 2016
まとめ
長い非コーディングRNA (lncRNA) とタンパク質をコードする遺伝子は隣接する遺伝子を調節することができます. これらの効果は,特定のRNA分子ではなく,一般的な転写プロセスから生じ,広範囲にわたる遺伝子クロストークを明らかにします.
科学分野:
- ゲノミクス
- 分子生物学
- 遺伝子規制
背景:
- 哺乳類のゲノムは長い非コーディングRNA (lncRNA) を大量に生成する.
- lncRNAは近くの遺伝子を局所的に調節すると仮定され,発現相関を説明する可能性がある.
- lncRNAトランスクリプトとは無関係な代替メカニズムもこれらの相関を誘導する可能性がある.
研究 の 目的:
- lncRNAロシが隣接する遺伝子発現に影響を与えるメカニズムを調査する.
- lncRNAトランスクリプトがこれらの調節効果を媒介するかどうかを決定する.
- タンパク質をコードする遺伝子にも同様の cis 調節メカニズムが適用されるかどうかを調べる.
主な方法:
- ネズミの細胞系を 遺伝子操作する
- lncRNAを生成する12のゲノムロキの分析
- タンパク質をコードする6つのロキのシス調節効果の評価
主要な成果:
- 12のlncRNAロシの5つが,シスにおける隣接遺伝子発現に影響を与えた.
- 規制効果は特定の lncRNA トランスクリプトとは無関係でした.
- メカニズムは,プロモーター増強剤の活性,転写,およびスプライシングを含む.
- タンパク質をコードする6箇所のうち4箇所は隣接する細胞にシス調節効果を示した.
結論:
- 遺伝子クロストークは,複数のシス調節メカニズムを含む一般的な現象です.
- lncRNAの産生ロキは,一般的な転写過程を通じて隣接する遺伝子に影響を与えることができます.
- これらの発見は,lncRNAsとタンパク質をコードする遺伝子の機能と進化の洞察を提供します.
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